Regulation of voltage-gated calcium channels by the ER calcium sensor STIM1

The endoplasmic reticulum (ER) Ca²⁺ sensor STIM1, best-known for its essential role in triggering influx of extracellular Ca²⁺ via Ca²⁺-release-activated channels when ER stores become depleted, unexpectedly also regulates Ca²⁺ entry through voltage-gated Ca²⁺ channels. In response to a drop in ER luminal Ca²⁺ level, this ER membrane-spanning sensor can contact voltage-gated Ca²⁺ channels in the plasma membrane and thereby inhibit Ca²⁺ influx through them. This previously unappreciated, interaction between ER Ca²⁺ level and magnitude of Ca²⁺ influx via voltage-gated Ca²⁺ channels may turn out to powerfully impact Ca²⁺ signaling in excitable cells, including neurotransmitter release, structural and functional postsynaptic plasticity, and transcription factor translocation.